Skip to main content
Archives of Disease in Childhood logoLink to Archives of Disease in Childhood
. 2005 Oct;90(10):1039–1044. doi: 10.1136/adc.2004.067272

Longitudinal relation between limited joint mobility, height, insulin-like growth factor 1 levels, and risk of developing microalbuminuria: the Oxford Regional Prospective Study

R Amin 1, T Bahu 1, B Widmer 1, R Dalton 1, D Dunger 1
PMCID: PMC1720121  PMID: 16177159

Abstract

Aims: To determine risk factors for development of microalbuminuria (MA) in relation to detection of limited joint mobility (LJM+) of the interphalangeal joints in a longitudinal cohort of type 1 diabetic (T1DM) subjects.

Results: After a median follow up of 10.9 years, 162 subjects (35.1%) developed LJM at median age 13.0 years and duration 5.2 years. More subjects developed LJM after compared to before puberty (67.6 v 32.4%). In LJM+ compared to LJM– subjects, HbA1c (mean 10.1 (SD 1.6) v 9.6 (1.4) %)) and ACR levels (median 1.1 (range 0.2–242.9) v 0.9 (0.4–70.7) mg/mmol) were higher, and in a Cox model probability of developing LJM was related to puberty and higher HbA1c levels. ACR levels were higher after detection of LJM compared to before (median 1.2 (range 0.4–102.6) v 0.8 (0.2–181.9) mg/mmol). Probability of developing MA was related to puberty, HbA1c, female sex, and presence of LJM (a 1.9-fold increased risk). Both LJM and MA were associated with lower height SDS (LJM: mean 0.0 (SD 1.0) v 0.2 (1.1); MA: 0.0 (1.0) v 0.2 (SD 1.0)) and lower IGF-1 levels.

Conclusion: The development of LJM was associated with an increased risk of microalbuminuria, independent of glycaemic control. Risk for both microalbuminuria and LJM was associated with puberty, reduced growth, and reduced IGF-1 levels, and may indicate underlying shared pathogenic mechanisms.

Full Text

The Full Text of this article is available as a PDF (96.9 KB).

Figure 1.

Figure 1

 Child with T1DM undertaking the prayer sign, showing mild LJM. Consent was obtained for publication of this figure.

Figure 2.

Figure 2

 Kaplan-Meier survival curve for probability of developing limited joint mobility.

Figure 3.

Figure 3

 (A) Height SDS; (B) Urine albumin:creatinine ratio (ACR) plotted against age in subjects with and without limited joint mobility (LJM). Figures derived from multi-level modelling, with thin lines representing ±SEM (see text for details).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Amin Rakesh, Schultz Carl, Ong Ken, Frystyk Jan, Dalton R. Neil, Perry Les, Ørskov Hans, Dunger David B., Oxford Regional Prospective Study Low IGF-I and elevated testosterone during puberty in subjects with type 1 diabetes developing microalbuminuria in comparison to normoalbuminuric control subjects: the Oxford Regional Prospective Study. Diabetes Care. 2003 May;26(5):1456–1461. doi: 10.2337/diacare.26.5.1456. [DOI] [PubMed] [Google Scholar]
  2. Amin Rakesh, Williams Rachel M., Frystyk January, Umpleby Margot, Matthews David, Orskov Hans, Dalton R. Neil, Dunger David B. Increasing urine albumin excretion is associated with growth hormone hypersecretion and reduced clearance of insulin in adolescents and young adults with type 1 diabetes: the Oxford Regional Prospective Study. Clin Endocrinol (Oxf) 2005 Feb;62(2):137–144. doi: 10.1111/j.1365-2265.2005.02185.x. [DOI] [PubMed] [Google Scholar]
  3. Arkkila P. E., Kantola I. M., Viikari J. S., Rönnemaa T., Vähätalo M. A. Limited joint mobility is associated with the presence but does not predict the development of microvascular complications in type 1 diabetes. Diabet Med. 1996 Sep;13(9):828–833. doi: 10.1002/(SICI)1096-9136(199609)13:9<828::AID-DIA182>3.0.CO;2-H. [DOI] [PubMed] [Google Scholar]
  4. Buckingham B., Perejda A. J., Sandborg C., Kershnar A. K., Uitto J. Skin, joint, and pulmonary changes in type I diabetes mellitus. Am J Dis Child. 1986 May;140(5):420–423. doi: 10.1001/archpedi.1986.02140190030018. [DOI] [PubMed] [Google Scholar]
  5. Chaturvedi N., Fuller J., Stephenson J. Short stature and diabetic nephropathy. BMJ. 1995 May 6;310(6988):1199–1199. doi: 10.1136/bmj.310.6988.1199b. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Clarke C. F., Piesowicz A. T., Spathis G. S. Limited joint mobility in children and adolescents with insulin dependent diabetes mellitus. Ann Rheum Dis. 1990 Apr;49(4):236–237. doi: 10.1136/ard.49.4.236. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cole T. J. The LMS method for constructing normalized growth standards. Eur J Clin Nutr. 1990 Jan;44(1):45–60. [PubMed] [Google Scholar]
  8. Danne T., Kordonouri O., Enders I., Hövener G., Weber B. Factors modifying the effect of hyperglycemia on the development of retinopathy in adolescents with diabetes. Results of the Berlin Retinopathy Study. Horm Res. 1998;50 (Suppl 1):28–32. doi: 10.1159/000053099. [DOI] [PubMed] [Google Scholar]
  9. Davis J. E., McDonald J. M., Jarett L. A high-performance liquid chromatography method for hemoglobin A1c. Diabetes. 1978 Feb;27(2):102–107. doi: 10.2337/diab.27.2.102. [DOI] [PubMed] [Google Scholar]
  10. Duffin A. C., Lam A., Kidd R., Chan A. K. F., Donaghue K. C. Ultrasonography of plantar soft tissues thickness in young people with diabetes. Diabet Med. 2002 Dec;19(12):1009–1013. doi: 10.1046/j.1464-5491.2002.00850.x. [DOI] [PubMed] [Google Scholar]
  11. Edge J. A., Dunger D. B., Matthews D. R., Gilbert J. P., Smith C. P. Increased overnight growth hormone concentrations in diabetic compared with normal adolescents. J Clin Endocrinol Metab. 1990 Nov;71(5):1356–1362. doi: 10.1210/jcem-71-5-1356. [DOI] [PubMed] [Google Scholar]
  12. Feldmann B., Jehle P. M., Mohan S., Lang G. E., Lang G. K., Brueckel J., Boehm B. O. Diabetic retinopathy is associated with decreased serum levels of free IGF-I and changes of IGF-binding proteins. Growth Horm IGF Res. 2000 Feb;10(1):53–59. doi: 10.1054/ghir.2000.0140. [DOI] [PubMed] [Google Scholar]
  13. Flyvbjerg A. Putative pathophysiological role of growth factors and cytokines in experimental diabetic kidney disease. Diabetologia. 2000 Oct;43(10):1205–1223. doi: 10.1007/s001250051515. [DOI] [PubMed] [Google Scholar]
  14. Frost D., Beischer W. Limited joint mobility in type 1 diabetic patients: associations with microangiopathy and subclinical macroangiopathy are different in men and women. Diabetes Care. 2001 Jan;24(1):95–99. doi: 10.2337/diacare.24.1.95. [DOI] [PubMed] [Google Scholar]
  15. Garg S. K., Chase H. P., Marshall G., Jackson W. E., Holmes D., Hoops S., Harris S. Limited joint mobility in subjects with insulin dependent diabetes mellitus: relationship with eye and kidney complications. Arch Dis Child. 1992 Jan;67(1):96–99. doi: 10.1136/adc.67.1.96. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Grgic A., Rosenbloom A. L., Weber F. T., Giordano B., Malone J. I., Shuster J. J. Joint contracture--common manifestation of childhood diabetes mellitus. J Pediatr. 1976 Apr;88(4 Pt 1):584–588. doi: 10.1016/s0022-3476(76)80011-x. [DOI] [PubMed] [Google Scholar]
  17. Haitas B., Jones D. B., Ting A., Turner R. C. Diabetic retinopathy and its association with limited joint mobility. Horm Metab Res. 1986 Nov;18(11):765–767. doi: 10.1055/s-2007-1012430. [DOI] [PubMed] [Google Scholar]
  18. Hovind Peter, Tarnow Lise, Rossing Peter, Jensen Berit Ruud, Graae Malene, Torp Inge, Binder Christian, Parving Hans-Henrik. Predictors for the development of microalbuminuria and macroalbuminuria in patients with type 1 diabetes: inception cohort study. BMJ. 2004 Apr 19;328(7448):1105–1105. doi: 10.1136/bmj.38070.450891.FE. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Huddle K. R., Gill G. V., Krige L. P. Limited joint mobility in Black patients with type I diabetes mellitus. S Afr Med J. 1983 Oct 1;64(15):579–581. [PubMed] [Google Scholar]
  20. Infante J. R., Rosenbloom A. L., Silverstein J. H., Garzarella L., Pollock B. H. Changes in frequency and severity of limited joint mobility in children with type 1 diabetes mellitus between 1976-78 and 1998. J Pediatr. 2001 Jan;138(1):33–37. doi: 10.1067/mpd.2001.109710. [DOI] [PubMed] [Google Scholar]
  21. Kakourou T., Dacou-Voutetakis C., Kavadias G., Bakoula C., Aroni K. Limited joint mobility and lipodystrophy in children and adolescents with insulin-dependent diabetes mellitus. Pediatr Dermatol. 1994 Dec;11(4):310–314. doi: 10.1111/j.1525-1470.1994.tb00094.x. [DOI] [PubMed] [Google Scholar]
  22. Larkin J. G., Frier B. M. Limited joint mobility and Dupuytren's contracture in diabetic, hypertensive, and normal populations. Br Med J (Clin Res Ed) 1986 Jun 7;292(6534):1494–1494. doi: 10.1136/bmj.292.6534.1494. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lieberman L. S., Rosenbloom A. L., Riley W. J., Silverstein J. H. Reduced skin thickness with pump administration of insulin. N Engl J Med. 1980 Oct 16;303(16):940–941. doi: 10.1056/nejm198010163031615. [DOI] [PubMed] [Google Scholar]
  24. McCance D. R., Crowe G., Quinn M. J., Smye M., Kennedy L. Incidence of microvascular complications in type 1 diabetic subjects with limited joint mobility: a 10-year prospective study. Diabet Med. 1993 Nov;10(9):807–810. doi: 10.1111/j.1464-5491.1993.tb00170.x. [DOI] [PubMed] [Google Scholar]
  25. Monnier V. M., Vishwanath V., Frank K. E., Elmets C. A., Dauchot P., Kohn R. R. Relation between complications of type I diabetes mellitus and collagen-linked fluorescence. N Engl J Med. 1986 Feb 13;314(7):403–408. doi: 10.1056/NEJM198602133140702. [DOI] [PubMed] [Google Scholar]
  26. Montaña E., Rozadilla A., Nolla J. M., Gomez N., Escofet D. R., Soler J. Microalbuminuria is associated with limited joint mobility in type I diabetes mellitus. Ann Rheum Dis. 1995 Jul;54(7):582–586. doi: 10.1136/ard.54.7.582. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Morrell D. J., Ray K. P., Holder A. T., Taylor A. M., Blows J. A., Hill D. J., Wallis M., Preece M. A. Somatomedin C/insulin-like growth factor I: simplified purification procedure and biological activities of the purified growth factor. J Endocrinol. 1986 Jul;110(1):151–158. doi: 10.1677/joe.0.1100151. [DOI] [PubMed] [Google Scholar]
  28. Penfold J., Chase H. P., Marshall G., Walravens C. F., Walravens P. A., Garg S. K. Final adult height and its relationship to blood glucose control and microvascular complications in IDDM. Diabet Med. 1995 Feb;12(2):129–133. doi: 10.1111/j.1464-5491.1995.tb00443.x. [DOI] [PubMed] [Google Scholar]
  29. Rosenbloom A. L., Malone J. I., Yucha J., Van Cader T. C. Limited joint mobility and diabetic retinopathy demonstrated by fluorescein angiography. Eur J Pediatr. 1984 Jan;141(3):163–164. doi: 10.1007/BF00443215. [DOI] [PubMed] [Google Scholar]
  30. Rosenbloom A. L., Silverstein J. H., Lezotte D. C., Richardson K., McCallum M. Limited joint mobility in childhood diabetes mellitus indicates increased risk for microvascular disease. N Engl J Med. 1981 Jul 23;305(4):191–194. doi: 10.1056/NEJM198107233050403. [DOI] [PubMed] [Google Scholar]
  31. Rosenbloom A. L., Silverstein J. H., Lezotte D. C., Riley W. J., Maclaren N. K. Limited joint mobility in diabetes mellitus of childhood: natural history and relationship to growth impairment. J Pediatr. 1982 Nov;101(5):874–878. doi: 10.1016/s0022-3476(82)80351-x. [DOI] [PubMed] [Google Scholar]
  32. Rossing P., Hougaard P., Borch-Johnsen K., Parving H. H. Predictors of mortality in insulin dependent diabetes: 10 year observational follow up study. BMJ. 1996 Sep 28;313(7060):779–784. doi: 10.1136/bmj.313.7060.779. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Rossing P., Tarnow L., Nielsen F. S., Boelskifte S., Brenner B. M., Parving H. H. Short stature and diabetic nephropathy. BMJ. 1995 Feb 4;310(6975):296–297. doi: 10.1136/bmj.310.6975.296. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Schultz C. J., Konopelska-Bahu T., Dalton R. N., Carroll T. A., Stratton I., Gale E. A., Neil A., Dunger D. B. Microalbuminuria prevalence varies with age, sex, and puberty in children with type 1 diabetes followed from diagnosis in a longitudinal study. Oxford Regional Prospective Study Group. Diabetes Care. 1999 Mar;22(3):495–502. doi: 10.2337/diacare.22.3.495. [DOI] [PubMed] [Google Scholar]
  35. Schultz C. J., Neil H. A., Dalton R. N., Konopelska Bahu T., Dunger D. B., Oxford Regional Prospective Study Group Blood pressure does not rise before the onset of microalbuminuria in children followed from diagnosis of type 1 diabetes. Oxford Regional Prospective Study Group. Diabetes Care. 2001 Mar;24(3):555–560. doi: 10.2337/diacare.24.3.555. [DOI] [PubMed] [Google Scholar]
  36. Silverstein J. H., Fennell R., Donnelly W., Banks R., Stratton R., Spillar R., Rosenbloom A. L. Correlates of biopsy-studied nephropathy in young patients with insulin-dependent diabetes mellitus. J Pediatr. 1985 Feb;106(2):196–201. doi: 10.1016/s0022-3476(85)80286-9. [DOI] [PubMed] [Google Scholar]
  37. Silverstein J. H., Gordon G., Pollock B. H., Rosenbloom A. L. Long-term glycemic control influences the onset of limited joint mobility in type 1 diabetes. J Pediatr. 1998 Jun;132(6):944–947. doi: 10.1016/s0022-3476(98)70388-9. [DOI] [PubMed] [Google Scholar]
  38. Vuković J., Dumić M., Radica A., Filipović-Grcić B., Jovanović V. Risk factors for expression and progression of limited joint mobility in insulin-dependent childhood diabetes. Acta Diabetol. 1996 Mar;33(1):15–18. doi: 10.1007/BF00571934. [DOI] [PubMed] [Google Scholar]
  39. le Pape A., Guitton J. D., Muh J. P. Modification of glomerular basement membrane cross-links in experimental diabetic rats. Biochem Biophys Res Commun. 1981 Jun 16;100(3):1214–1221. doi: 10.1016/0006-291x(81)91953-7. [DOI] [PubMed] [Google Scholar]

Articles from Archives of Disease in Childhood are provided here courtesy of BMJ Publishing Group

RESOURCES